IMPAACT 2015 - Evaluation of the HIV-1 Reservoir in the Central Nervous System of Perinatally-Infected Youth and Young Adults With Cognitive Impairment

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IMPAACT 2015 is a cross-sectional, exploratory study that will investigate the central nervous system (CNS) reservoir in perinatally HIV-infected adolescents and young adults on effective antiretroviral therapy with neurocognitive impairment. The study will assess the frequency with which HIV is detected in the cerebral spinal fluid (CSF) in this population and assess whether detectable HIV in the CSF correlates with markers of inflammation and neuronal injury. Findings from this study will advance understanding of the role of the CNS in HIV-1 persistence and its implications for future HIV-1 remission research.

Condition or disease

HIV-1-infection

Detailed Description:

IMPAACT 2015 is a cross-sectional, exploratory study aiming to investigate the central nervous system (CNS) reservoir in perinatally HIV-infected adolescents and young adults on effective antiretroviral therapy with neurocognitive impairment. The study will assess the frequency with which HIV is detected in the cerebral spinal fluid (CSF) in this population and assess whether detectable HIV in the CSF correlates with markers of inflammation and neuronal injury. CSF will be examined for persistence of HIV-1 RNA or DNA despite antiretroviral therapy (ART) and for evidence of intrathecal inflammation. Perinatally-infected youth and young adults are of particular interest because there are very limited CSF data available in this population and reasons to be concerned about the CNS reservoir. In addition, measures of HIV-1 RNA in the CSF and associated biomarkers have not previously been explored in this population. A better understanding of viral persistence in the CSF, as well as CSF biomarker profiles, will provide preliminary data to move the field forward in understanding the role of the CNS in HIV-1 persistence and will have implications for future HIV-1 remission research.

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Layout table for eligibility information

Ages Eligible for Study:

13 Years to 24 Years (Child, Adult)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Sampling Method:

Non-Probability Sample

Study Population

Perinatally HIV-1-infected youth and young adults (13-24 years of age) with cognitive impairment, on suppressive antiretroviral therapy, from study sites in the United States

Criteria

Inclusion Criteria:

13-24 years of age (inclusive) at enrollment (i.e., on the day the participant is enrolled in the study)

Spoken fluency in English or Spanish

If not of legal age to provide independent informed consent: Parent or legal guardian, or other legally authorized representative is willing and able to provide written informed consent for study participation and potential participant is willing and able to provide written assent for study participation

If of legal age but not able to provide independent informed consent due to cognitive impairment as determined by site standard operating procedures (SOPs) and consistent with site institutional review board/ethics committee (IRB/EC) policies and procedures: Parent, legal guardian, or other legally authorized representative is willing and able to provide written informed consent for study participation and potential participant is willing and able to provide written assent for study participation

If of legal age and able to provide independent informed consent as determined by site SOPs and consistent with site IRB/EC policies and procedures: Willing and able to provide written informed consent for study participation

Has confirmed perinatal HIV-1 infection — with no documented evidence to suggest another route of transmission — based on review of available medical records

Has been taking combination ART comprised of at least three agents from at least two classes of antiretroviral therapy for at least 12 consecutive months prior to enrollment as determined by the site investigator or designee based on participant or parent/guardian report and available medical records; regimen changes within the 12 months prior to enrollment are permitted, provided the virologic requirements in criterion below are met

Has at least two consecutive documented plasma HIV-1 RNA values less than 40 copies/mL, at least three months apart, in the 12 months prior to enrollment; one of these values must be based on testing of a specimen collected within the 60 days prior to enrollment

Has a Fluid Cognition Composite Score at least one-and-a-half standard deviations below the published normative mean (i.e., less than 78) based on administration of the NIH Toolbox Cognition Battery

Exclusion Criteria:

Any ART interruption for more than seven consecutive days in the 12 months prior to enrollment

Any HIV-1 RNA value greater than 200 copies/mL in the 12 months prior to enrollment

Completed any of the NIH Toolbox subtests specified within 90 days prior to screening

Any documented full scale intelligence quotient (IQ) score more than three standard deviations below the published normative mean (i.e., less than 55) or a Fluid Cognition Composite Score more than three standard deviations below the published normative mean (i.e., less than 55) based on administration of the NIH Toolbox Cognition Battery at screening

Any documented diagnosis of autism spectrum disorder, schizophrenia, or other psychotic disorder

Any known prior infection of the CNS that may be persistent or recurrent (e.g., cryptococcal meningitis, neurosyphilis)

Any known non-HIV-related cause or significant contributing factor for cognitive impairment (e.g., birth injury, head injury, stroke, major or mild neurocognitive disorder due to a condition other than HIV) per Diagnostic and Statistical Manual of Mental Disorders 4th Edition (DSM-V) criteria

If female and of reproductive potential (defined as having experienced menarche and having no documented history of a sterilization procedure), known or suspected pregnancy

Any serious or otherwise clinically significant infection of the CNS or bloodstream (other than HIV-1 infection) within 30 days prior to enrollment

Any live vaccine received within 30 days prior to enrollment

Any other (non-live) vaccine received within 7 days prior to enrollment

Received prolonged (more than 14 days) or high dose immunosuppressants within 30 days prior to enrollment (high dose would include >1 mg/kg prednisone (or equivalent) or any biologic immunosuppressant such as monoclonal antibody based therapy)